Oncogen

Oncogen Limited Partnership

Bristol-myers Squibb Compnay

Duke University

Oncogen, a Limited Partnership

Hans Marquardt

Mohammed Shoyab

George J Todaro

Ingegerd E Hellstrom

Karl E Hellstrom

Peter S Linsley

Joyce M Zarling

Marcia B Hanson

Barton F Haynes

Alejandro A Aruffo

Daniel R Twardzik

Thomas J Brown

Michael A Bowen

Dhavalkumar D Patel

Martha S Hayden

Peter C Su

Anthony W Siadak

Joseph P Brown

Clay B Siegall

Anthony F Purchio

Timothy M Rose

Mario N Lioubin

Tatsuhiko Ikeda

Stephen McAndrew

Yoshitaka Yoneyama

Janet Johnston

Najma Malik

Susan L Gawlak

Ursula Garrigues

The present invention relates, in general, to CD6 and, in particular, to a CD6 ligand present on the surface of thymic epithelial cells, monocytes, activated T cells and a variety of other cell types. The invention further relates to methods of inhibiting the interaction of CD6 and the CD6 ligand, and to methods of screening compounds for their ability to inhibit that interaction. The invention also relates to antibodies, and binding fragments thereof, specific for CD6 ligand.

Anti-CD6 ligand antibodies

The present invention relates to an isolated nucleic acid molecule having a sequence that encodes a CD6 ligand present on the surface of thymic epithelial cells, monocytes, activated T cells and a variety of other cell types. The invention further relates to a construct containing the nucleic acid molecule and to a host cell comprising same. Further, the invention relates to a method of producing a CD6 ligand.

CD6 ligand encoding sequence

The present invention provides internalizing ligands (i.e., BR110 ligands) which specifically recognize and bind the BR110 antigen. After binding the antigen, the ligand and antigen form a complex. As a complex, the antigen can be detected using well known and developed methods and commercial systems.

Monoclonal antibody BR110 and uses thereof

Novel compositions comprising Oncostatin M and congeners thereof, as well as methods for their preparation and methods for their use are provided. The compositions may be prepared by isolation from natural sources, or by recombinant means in either prokaryotic or eukaryotic host cells. In addition, the DNA and polypeptide sequences for Oncostatin M are disclosed. The compositions find use in modulating growth of cells, in particular inhibition of tumor cell proliferation, and stimulation of normal cell growth, especially cells involved in hematopoiesis. Cell growth inhibition compositions may additionally include an adjunctive agent comprising at least one of a transforming growth factor, tumor necrosis factor, or an interferon. Receptors having high affinity for Oncostatin M may additionally be used to screen polypeptides for Oncostatin M-like activity. Methods for use of antibodies to the compositions and probes specific for Oncostatin M mRNA as a means for detecting tumor cells are also provided.

Oncostatin M and novel compositions having anti-neoplastic activity

The present invention discloses a new ribosome-inactivating protein, bryodin 2, isolated from the plant Bryonia dioica. This ribosome-inactivating protein (RIP) is a type IRIP having a single polypeptide chain and no cellular receptor domain. Like many type I RIPs, bryodin 2 has a molecular weight of about 27,000 daltons and a pI of 9.5. Bryodin 2 differs from previously identified ribosome-inactivating protein in its amino acid composition, amino acid sequence, and toxicity in vitro and in vivo. Bryodin 2 is useful, as are other type I ribosome-inactivating proteins, as an abortifacient, immunomodulator, anti-tumor or anti-viral agent. Compositions comprising bryodin 2 as an immunoconjugate or fusion molecule are particularly useful to kill cells of a target population.

Bryodin 2 a ribosome-inactivating protein isolated from the plant

Thermally stable cytosine deaminase (CDase), and the gene coding therefor, is disclosed as well as methods of isolating, purifying, and recombinantly producing the same. The thermally stable CDase can be isolated from Saccharomyces cerevisiae. The yeast isolated enzyme has a molecular weight of approximately 32 kDa, as determined by gel filtration chromatography, and is composed of two subunits, each with a molecular weight of about 17 kDa. Thermally stable yeast CDase so purified shows no significant sequence homology with other known sequenced proteins.

Thermally stable cytosine deaminase from saccharomyces

The present invention is concerned with novel monoclonal antibody L53 which binds strongly to a glycoprotein antigen associated with human tumors, including carcinomas of the colon, breast, and lung, as well as melanomas. The antibody binds to normal human cells to a much lesser degree than to tumor cells. The antibody finds use in diagnostic methods for as the detection of malignant cells associated with tumors. Also disclosed is a novel 70,000-75,000 dalton glycoprotein antigen recognized by MAb L53. The L53 antigen is found on the cell surface of human tumor cells. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

Monoclonal antibody L53 which recognizes a human tumor-associated antigen

Expression of DNA sequences encoding a thermally stable cytosine

The present invention is concerned with novel monoclonal antibodies which bind strongly to a protein antigen associated with human non-small cell lung carcinomas ('NSCLC') human small cell lung carcinomas and certain other human carcinomas including many carcinomas of the colon and breast. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use both in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods for treatment of human in NSCLC and certain other human carcinomas. Also disclosed is a novel 110,000 dalton glycoprotein antigen found on the cell surface of human non-small lung carcinoma tumor cells and on cells from certain other human cancers. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

Monoclonal antibodies and antigen for human non-small cell lung

The present invention is concerned with a novel monoclonal antibody which binds strongly to a protein antigen associated with human tumors, including carcinomas of the colon and lung. The antibody binds to normal human cells to a much lesser degree than to tumor cells. The antibody finds use both in diagnostic methods such as the detection of malignant cells associated with tumors and in therapeutic methods for treatment of humans with tumors. Also disclosed is a novel 66,000 dalton glycoprotein antigen found on the cell surface of human tumor cells. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

Monoclonal antibody to novel antigen associated with human tumors

The present invention is concerned with a novel monoclonal antibody which binds strongly to a protein antigen associated with human tumors, including carcinomas of the colon, breast, ovary and lung, as well as melanomas and sarcomas. The antibody binds to normal human cells to a much lesser degree than to tumor cells. The antibody finds use both in diagnostic methods such as the detection of malignant cells associated with tumors and in therapeutic methods for treatment of humans with tumors. Also disclosed is a novel 100,000 dalton glycoprotein antigen found on the cell surface of human tumor cells. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

Novel compositions are provided for modulating growth, particularly of tumor cells, which compositions are combinations of Oncostatin M, and one or both of transforming growth factors or .gamma.-interferons, or analogs thereof. In addition, a novel transforming growth factor is provided, designated TGF-.beta.2, as well as methods for its preparation.

Novel polypeptides, polynucleotide sequences, DNA constructs and compositions are provided for the preparation and use of polypeptides associated with naturally occurring polypeptides found in brains. The low molecular weight polypeptides either are growth inhibitors for neoplastic cells without inhibiting normal cells or affect GABA-ergic transmission. The polypeptides find use in inhibiting neoplastic growth, modulating diazepam receptor response, and detecting receptors for the polypeptides. Antibodies are provided in conjunction with the polypeptides, which may be used together or separately for detecting the presence of the polypeptides.

Growing community of inventors

Mercer Island, WA, United States of America

Hans Marquardt